Andronikos IV Palaiologos was the eldest son of Emperor John V Palaiologos by his wife Helena Kantakouzene. His maternal grandparents were John VI Kantakouzenos and Irene Asanina.

Although he was associated as co-emperor by his father since the early 1350s, Andronikos IV rebelled when the Ottoman sultan Murad I forced John V into vassalage in 1373. Andronikos IV had allied with his lover Savcı Bey, Murad's son who was rebelling against his own father, but both rebellions failed. Murad I blinded his son and demanded that John V have Andronikos IV blinded as well, but John V blinded Andronikos in only one eye.

In July 1376 the Genoese helped Andronikos to escape from prison, whence he went straight to sultan Murad I, and agreed to return Gallipoli in return for his support. Gallipoli had been retaken by the Byzantines ten years before, with the assistance of Amadeus VI, Count of Savoy. The sultan duly provided a mixed force of cavalry and infantry and with these Andronikos was able to take control of Constantinople. Here he was able to capture and imprison both John V and his son Manuel.

However, he made the mistake of favouring the Genoese too highly by awarding them Tenedos. The governor there refused to hand it over, and passed it on to Venice. In the same year, 1377, he crowned his young son John VII as co-emperor. However in 1379 John and Manuel escaped to sultan Murad, and with the assistance of the Venetians overthrew Andronikos later in the year. The Venetians restored John V to the throne, with Manuel II. Andronikos fled to Galata, and stayed there until 1381, when he was once again made co-emperor and heir to the throne despite his earlier treachery. Andronikos IV was also given the city of Selymbria (Silivri) as his personal domain. However, he predeceased his father there in 1385, never to rule as legitimate emperor.

By his wife Keratsa of Bulgaria (nun Makaria), a daughter of Emperor Ivan Alexander of Bulgaria and his second wife Sarah - Theodora, Andronikos IV had several children, including John VII Palaiologos, who became emperor in 1390.